A nerve carries the peripheral processes (or axons) of neurons. The neuronal cell bodies reside in the spinal cord (motor neurons), in ganglia situated along the vertebral column (spinal sensory ganglia) or in ganglia found throughout the organs of the body (autonomic and enteric ganglia). A nerve consists of axons, Schwann cells and extensive connective tissue sheaths (Dagum A B (1998) J Hand Ther 11:111-117). The outer covering, the epineurium, is made of collagenous connective tissue that cushions the fascicles from external pressure and surrounds the perineurium. The perineurium surrounds the individual fascicles and, together with endothelial cells in the endoneurial microvessels, functions as the blood-nerve barrier. The endoneurium lies inside the perineurium and consists of collagenous tissue that surrounds the Schwann cells and axons. A fascicular group consists of two or more fascicles surrounded, respectively, by perineurium and epineurium. The topography of nerves is constant distally, with a group of fascicles being either sensory or motor. The neuron consists of a soma (cell body) and an axon, which can be several feet long.
Nerve injuries are a major source of chronic disability. Poor management of nerve injuries is associated with muscle atrophy and can lead to painful neuroma when severed axons are unable to reestablish continuity with the distal nerve. Although nerves have the potential to regenerate after injury, this ability is strictly dependent upon the regenerating nerve fibers making appropriate contact with the severed nerve segment. Regenerating axons that fail to traverse the gap or injury site and enter the basal lamina of the severed distal nerve segment will deteriorate, resulting in neuronal death, muscle atrophy and permanent functional deficit (Fawcett J W et al. (1990) Annu Rev Neurosci 13:43-60).
In nerve injuries where there is axonal disruption, but the continuity of the endoneurial sheath remains intact (e.g., crush injury), axons regenerate within their original basal lamina and complete recovery can be expected. In contrast, axonal regrowth may be severely compromised after nerve transection and surgical repair is highly dependent on the realignment of the nerve elements described above (Dagum A B (1998) J Hand Ther 11:111-117).
Numerous methods of nerve coaptation have been tested and applied, including various suture methods, adhesives, laser treatments, and conduits. Nerve repair with sutures is standard practice. The use of sutures provides a long-lasting union but has limitations and complications. For example, sutures can elicit a foreign body reaction, impair vascularity, and potentially disrupt axonal regeneration. Therefore, coaptation of severed nerves without sutures would be desirable and could potentially eliminate the tissue trauma associated with traditional suturing techniques.
A variety of sutureless nerve repair methods have been explored including the use of biological glues. The advantages of gluing techniques include the potential for simple application and rapid repair time. Coaptation by gluing has the potential to be more efficient, eliminate variables of tension due to suture placement and technique, and improve alignment of fascicles.
Fibrin glue has been tested most extensively as a biological adhesive. Unfortunately, fibrin glue has insufficient adhesive and tensile strength to ensure a secure nerve union for most nerve repairs. Fibrin glue repairs are prone to dehiscence (Cruz et al., 1986; Maragh et al., 1990) and mechanical testing shows it imparts negligible strength to a nerve coaptation (Temple et al., 2004). In addition to its lack of adhesive strength, fibrin glue is rapidly degraded and is completely absorbed within several days in vivo. Therefore, repair with fibrin glue alone is unreliable and rarely performed.
Several glues with high adhesive and tensile strength have been developed. Polyethylene glycol (PEG) based hydrogels have been explored in tissue repair applications. PEG-hydrogels bind strongly to tissues and act as effective sealants (Preul et al., 2003). PEG-hydrogels do not provide a good substrate for cell attachment and growth, and can have desirable effect on the inhibition of tissue-tissue adhesions that often occur after surgical repair (Hem et al., 1998). This same property indicates that PEG-hydrogels must be applied judiciously as to not interfere with cell migration required for tissue regeneration. PEG-hydrogels have been explored in neural tissue repair and reconstruction (Woerly, 1993). The main goal of these repair studies is to derivatize or otherwise alter the hydrogels to support cell adhesion. Hydrogels are marketed as sealants. A successful product, DuraSeal (Confluent Surgical, Inc.), is used to prevent the leakage of fluid from the dura after repair with sutures.